We previously demonstrated that a portion of the circulating thyroid hormones in humans is associated with each of the plasma lipoproteins, VLDL, LDL and HDL. We now have shown that this interaction is the result of binding to apolipoproteins. In HDL, the major lipoprotein carrier, apoA-I and apoC-II and/or apoC-III account for this binding. In VLDL and LDL, binding is to apoB-100. The stereospecificity of the interactions are different from those of the other T4-binding proteins in plasma, and the affinity is decreased by lipids. The latter accounts for the fact that the major lipoprotein carrier of thyroid hormone is a 68 kDa subfraction of HDL. This newly identified species was previously found as a contaminant in TBG preparations. The interactions of thyroid hormones with lipoproteins may provide a special mechanism for the entry of T4 and T3 into certain types of cells.